Prostate cell cultures as in vitro models for the study of normal stem cells and cancer stem cells

Abstract

Current existing therapies for prostate cancer eradicate the majority of cells within a tumor. However, most patients with advanced cancer still progress to androgen-independent metastatic disease that remains essentially incurable by current treatment strategies. Recent evidence has shown that cancer stem cells (CSCs) are a subset of the tumor cells that are responsible for initiating and maintaining the disease. Understanding normal stem cells and CSCs may provide insight into the origin of and new therapeutics for prostate cancer. Normal stem cells and CSCs have been identified in prostate tissue by the use of several markers or techniques. Although research on stem cells has been limited by the lack of suitable in vitro systems, recent studies show that not only primary cells but also several established cell lines may exhibit stem cell properties. This review discusses various in vitro culture systems to propagate normal prostate stem cells and prostate CSCs together with molecular markers. These in vitro cell culture models should be useful for elucidating the differentiation of prostatic epithelium and the biological features of prostate cancer.

In vitro model systems to study androgen receptor signaling in prostate cancer

“…Whilst it is generally preferable to isolate PCSCs from primary cancer cells rather than PCa cell lines, tissue availability is often a limiting factor. Interestingly, several established PCa cell lines such as LNCaP, LAPC-4 and C4-2 may also contain CD44 C PCSCs (Miki & Rhim 2008, Lee et al 2013. Further studies are required to determine whether established PCa cell lines contain bona fide PCSCs and to assess the functional contribution of AR signaling on PCSC behavior.…”

The Role of Cancer Stem Cells and MicroRNAs in Human Prostate Cancer

“…The molecular markers of prostatic epithelial cells are characterized to identify the origin of normal and CSCs (Lawson & Witte, 2007). The androgen dependent luminal secretory cells express AR, prostate specific antigen, prostatic acid phosphatase, CD57, and low molecular weight cytokeratin (Miki & Rhim, 2008). The androgen independent non-secretory basal cells do not express androgen receptor (or low levels of AR), prostate specific antigen or prostatic acid phosphatase but present CD44, p63, and high molecular weight cytokeratin.…”

“…The androgen independent non-secretory basal cells do not express androgen receptor (or low levels of AR), prostate specific antigen or prostatic acid phosphatase but present CD44, p63, and high molecular weight cytokeratin. The normal stem cells among basal cells amplify to differentiate into androgen independent transit amplifying cells (TACs) and these cells further differentiate to form androgen dependent luminal cells (Miki & Rhim, 2008;Wang & Shen, 2011).…”

“…The luminal cells stay above basal cell layer and function to secrete prostate specific molecules through luminal space. The prostatic stem cells are commonly present in these epithelial cell populations, especially in basal cell subpopulation (Lawson & Witte, 2007;Miki & Rhim, 2008). The molecular markers of prostatic epithelial cells are characterized to identify the origin of normal and CSCs (Lawson & Witte, 2007).…”

Connexins and Cadherin Cross-talk in the Pathogenesis of Prostate Cancer

“…This screen revealed that all the prostate cancer cell lines that we screened expressed E-cadherin or N-cadherin endogenously ( Figure 3). The characteristics of these cell lines have been described [25][26][27][28][29][30]. This prohibited us from undertaking the proposed studies in task 2 because the available antibodies for Ecadherin do not distinguish the endogenously expressed E-cadherin from exogenously expressed E-cadherin constructs.…”